PROJECT SUMMARY/ABSTRACT This project is designed to reveal basic principles of olfactory system function. It investigates the logic that connects odor receptor responses to behavioral responses in a numerically simple olfactory system. The experimental plan takes advantage of the Drosophila larva, which contains 21 olfactory receptor neurons and ~21 functional odor receptors. This system allows incisive molecular genetic analysis as well as convenient behavioral analysis. The first specific aim proposes analysis of the sensory input into the larval olfactory system. It considers the sensitivity, tuning, and diversity of the entire larval receptor repertoire, analyzed in a functional expression system. Particular attention is paid to a special class of remarkably long-lasting physiological responses, or supersustained responses. The second aim proposes analysis of the behavioral output of the system. The behavior elicited by the most effective odor for each receptor is measured, determining whether each odor produces attraction or repulsion. The behavior elicited by pairs of odors is then analyzed. An important goal is to examine the additivity of odors that activate distinct subsets of receptors, and to compare it to the additivity of odors that activate overlapping subsets of receptors. The third aim concerns the molecular and cellular logic by which the sensory input is translated into the behavioral output. An attractive response is analyzed to determine whether it consists of discrete elements that depend on different receptors. Repellent responses are investigated to determine whether they depend on excitation or inhibition of particular receptors. The final aim examines supersustained physiological responses and determines whether these long- lasting responses compromise the ability of an animal to locate an odor source. The results may advance our understanding of the information flow through a simple model olfactory system. The results may also have special implications for the control of insect vectors of disease. Hundreds of millions of people each year suffer from diseases transmitted by insects, many of which locate humans through olfactory cues. An improved understanding of the principles of insect olfaction could lead to improved means of controlling these insects and the diseases they transmit.